Integrated Clinical and Prognostic Analysis of the m(6)A RNA Methylation Regulator YTHDF3 in Pan-Cancer and its Correlation with Cancer Cell Proliferation.
Integrated Clinical and Prognostic Analysis of the m(6)A RNA Methylation Regulator YTHDF3 in Pan-Cancer and its Correlation with Cancer Cell Proliferation.
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m6A RNA 甲基化调节因子 YTHDF3 在泛癌中的综合临床和预后分析及其与癌细胞增殖的相关性
DOI：
10.7150/jca.78403
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发表时间：
2022
影响因子：
3.9
通讯作者：
Ma, Lifang
中科院分区：
文献类型：
--
作者：
Cao, Leiqun;Zeng, Bingjie;Wang, Yulan;Wang, Xianzhao;Qin, Yueyang;Zhang, Congcong;Wu, Mengyi;Wang, Jiayi;Zhang, Xiao;Ma, Lifang
背景：N6-甲基腺苷(M6A)是哺乳动物RNA分子中含量最丰富、范围最广的化学修饰。虽然许多研究已经研究了m6A甲基化相关基因，但就我们所知，还没有研究YTH N6-甲基腺苷RNA结合蛋白3(YTHDF3)在癌症中的表达模式。方法：利用各种公开可用的数据集，我们在33种肿瘤类型中寻找YTHDF3的潜在致癌作用。此外，还包括临床病理参数、临床预后价值、浓缩分析、突变、微卫星不稳定性(MSI)、肿瘤突变负荷(TMB)、浸润性细胞水平和相关免疫检查点基因。最后，我们利用现有的临床样本和与增殖相关的功能实验进行了验证性分析。结果：YTHDF3在大多数肿瘤组织中高表达，在某些肿瘤中与患者预后相关。ROC分析表明，YTHDF3对13种癌症具有较高的诊断价值。此外，我们还发现与YTHDF3相关的基因在翻译起始和mRNA代谢过程中都得到了丰富。GSEA检测结果表明，YTHDF3可能与不同肿瘤类型的细胞内不同途径有关。我们进一步分析了YTHDF3的表达与MSI、TMB和免疫检查点基因的相关性。YTHDF3还可能发挥重要的抗肿瘤免疫治疗作用。此外，TIMER的免疫分析结果显示，泛癌组织中YTHDF3的高表达水平与免疫抑制的微环境有关。最后，我们通过实验证明了YTHDF3的过度表达和下调都会影响癌细胞的增殖率。结论：YTHDF3是一种很有前途的肿瘤诊断生物标志物。这项研究提供了关于YTHDF3的第一个全面的泛癌症报告，并增加了我们对其在不同肿瘤中的致癌作用的理解。
Background: N6-methyladenosine (m6A) is the most abundant and extensive chemical modification of mammalian RNA molecules. Although numerous studies have investigated m6A methylation-related genes, to the best of our knowledge, none have examined the expression patterns of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) across cancers. Methods: Using various publicly available datasets, we searched for a potential carcinogenic role of YTHDF3 in 33 tumor types. Furthermore, the clinicopathological parameters, clinical prognostic value, enrichment analysis, mutations, microsatellite instability (MSI), tumor mutation burden (TMB), levels of infiltrating cells, and related immune checkpoint genes were included. Finally, we performed a validation analysis using existing clinical samples and proliferation-related functional experiments. Results: YTHDF3 is highly expressed in most cancer types and associated with patient prognosis in certain tumors. The ROC analysis suggested that YTHDF3 has high diagnostic value in 13 types of cancer. Furthermore, we found that the genes associated with YTHDF3 were enriched for translation initiation and mRNA metabolic processes. The results of the GSEA enrichment suggest that YTHDF3 may be associated with different pathways in cells in various tumor types. We further analyzed the correlations between YTHDF3 expression and MSI, TMB, and immune checkpoint genes. YTHDF3 also possibly exerts important antitumor immunotherapy effects. Additionally, the results of the immune analysis using TIMER showed that high YTHDF3 expression levels in pan-cancer tissues were related to an immunosuppressive microenvironment. Finally, we experimentally demonstrated that both overexpression and downregulation of YTHDF3 can affect cancer cell proliferation rates. Conclusion: YTHDF3 is a promising biomarker for cancer diagnosis. This study provides the first comprehensive pan-cancer report on YTHDF3 and increases our understanding of its oncogenic role in different tumors.
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影响因子：
16.6
作者：
Bawankar P;Lence T;Paolantoni C;Haussmann IU;Kazlauskiene M;Jacob D;Heidelberger JB;Richter FM;Nallasivan MP;Morin V;Kreim N;Beli P;Helm M;Jinek M;Soller M;Roignant JY
通讯作者：
Roignant JY
Mettl14通过Notch1的N-6-甲基腺苷抑制膀胱TIC自我更新和膀胱肿瘤发生
影响因子：
37.3
作者：
Gu, Chaohui;Wang, Zhiyu;Tian, Fengyan
通讯作者：
Tian, Fengyan
影响因子：
15
作者：
Rauch S;He C;Dickinson BC
通讯作者：
Dickinson BC
影响因子：
16.6
作者：
Price AM;Hayer KE;McIntyre ABR;Gokhale NS;Abebe JS;Della Fera AN;Mason CE;Horner SM;Wilson AC;Depledge DP;Weitzman MD
通讯作者：
Weitzman MD
DOI：
10.1126/science.aau1646
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Frye M;Harada BT;Behm M;He C
通讯作者：
He C